31P MRS has been used to non-invasively assess the effects of MgSO4 compared to Na2SO4 infusions on brain phosphorylated compounds and intracellular pH (pHi) before, during and after hypoxia-ischemia. Swine were infused with either MgSO4 or equivalent volumes of Na2SO4 and each group underwent hypoxia-ischemia. Evaluation of systemic physiologic variables indicated that the groups were well matched. 31P MRS provides the ability to determine intracellular ionized Mg concentration [Mg]i non-invasively by quantitating the Mg-dependent changes in the frequency of the 31P MR signal from the phosphorus atoms of NTP. Calculated [Mg]i was similar between groups at control and significantly increased relative to control in both groups during hypoxia-ischemia. However, there were group differences with higher values of [Mg]i during hypoxia-ischemia in the MgSO4 infused compared to the Na2SO4 infused animals. Following hypoxia-ischemia there was a longer time for [Mg]i to return to baseline values in MgSO4 compared to Na2SO4 infused mini-swine. There are three potential reasons for the group differences in [Mg]i. First, the greater intracellular acidosis during and following hypoxia-ischemia in MgSO4 compared to Na2SO4 animals could reduce binding of Mg to cellular proteins and result in an elevated ionized fraction. Second, hydrolysis of NTP during brain energy failure from hypoxia-ischemia would be expected to free Mg normally complexed to NTP. This could contribute to the greater increase in [Mg]i of MgSO4 animals since this group experienced a greater reduction in NTP compared to Na2SO4 infused animals. Finally, it could be speculated that there is movement of Mg from the extracellular to the intracellular compartment. Although alterations in [Mg]i remain incompletely understood, the observed changes indicate that Mg may be influencing important variables not only externally at the cell surface via changes in extracellular fluid [Mg], but also within the cell itself. (Service 11) REPORT PERIOD: (09/01/97-08/31/98)